The compound N-[4-[[4-(diethyl amino) phenyl](2,5-disulfophenyl)methylene]-2,5-cyclohexadien-1-ylidene]-N-ethylethanaminium inner salt sodium salt (Isosulfan blue) is represented by the formula (I)

Isosulfan blue (I) is a triarylmethane dye used as a contrast agent for delineation of lymphatic vessels and is particularly useful as a cancer diagnostic agent. Isosulfan blue is marketing as lymphazurin blue dye, which is available as 1% (10 mg/ml) 5 ml solution for injection.
U.S. Pat. Nos. 1,531,507, 7,534,911, 8,969,616 reported various processes for the synthesis of dyes specifically, Isosulfan blue, the contents of which are hereby incorporated as reference in their entirety.
General synthesis of Isosulfan blue was first described in the U.S. Pat. No. 1,531,507. According to this Isosulfan blue is made by converting orthochlorobenzaldehyde to sodium salt of 2-chlorobenzaldehyde-5-sulfonic acid by sulphating using oleum (26% or oleum 65%) and sodium carbonate, which is further treated with sodium sulphite to produce benzaldehyde-2,5-disulfonic acid sodium salt followed by condensation with alkylated aryl amine to produce isoleuco compound. The obtained compound is oxidised to produce Isosulfan blue. The yield and purity of the final compound is not reported in the known art.
U.S. Pat. No. 7,534,911 patent discloses another route for the synthesis of Isosulfan blue (Scheme-1) by sulphonating orthochlorobenzaldehyde with Oleum (23% to 65%) to obtain 2-chlorobenzaldehyde-5-sulfonic acid, which is subsequently treated with sodium sulphite and followed by basification produces sodium salt of benzaldehyde-2,5-disulfonic acid sodium. This is further treated with sodium sulphite to get disodium salt followed by condensation with diethyl aniline to yield sodium 2-(bis(4-(diethylamino)phenyl)methyl)benzene-1,4-disulfonate and oxidizing the obtained compound with ammonium dichromate in presence of sulphuric acid affords Isosulfan blue.

U.S. Pat. No. 8,969,616 discloses another route of synthesis of synthesis for Isosulfan blue (Scheme-2). In this Isosulfan blue is obtained by the reaction of 4-Chloro-3-formylbenzenesulfonic acid with sodium sulphite and sodium sulphite mixture in presence of water at very high temperature (180° C.) under high pressure (150 PSI) by isolating the crude with huge volumes of methanol further underwent purifications using huge volumes of Dimethylformamide and Dichloromethane solvent to get pure compound and ends in very low yield to get Sodium-2-formylbenzene-1,4-disulfonate. Further reaction of Sodium-2-formylbenzene-1,4-disulfonate with diethyl aniline in presence of urea and acetic acid at reflux temperature for longer hours (20-25 hrs) then isolated by cooling the reaction mixture followed by addition of anti-solvent methanol to give crude 2-(Bis(4-(diethylamino)phenyl) methyl)benzene-1,4-disulfonic acid. The isolated crude underwent purifications to give pure 2-(Bis(4-(diethylamino)phenyl)methyl)benzene-1,4-disulfonic acid. The 2-(Bis(4-(diethylamino)phenyl)methyl)benzene-1,4-disulfonic acid gets oxidized in presence of silver oxide in methanol media and further isolation using Diisopropylether to obtain Isosulfan blue.

Therefore, there is a need in the art for an improved method for the preparation of Isosulfan blue in significantly high yield and purity. In view of this, the present inventors provide a safe and cost-effective process for the preparation of Isosulfan blue in significantly high yield.